Phase-3 Randomized Controlled Trials on Exclusion of Participants With Kidney Disease in COVID-19.
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ABSTRACT:
SUBMITTER: Chewcharat A
PROVIDER: S-EPMC7577277 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Objective: Post-randomisation exclusions in randomised controlled trials are common and may include participants identified as not meeting trial eligibility criteria after randomisation. We report how a decision might be reached and reported on, to include or exclude these participants. We illustrate using a motivating scenario from the BREATHE trial (Trial registration ClinicalTrials.gov, NCT02426112) evaluating azithromycin for the treatment of chronic lung disease in people aged 6-19?years with HIV in Zimbabwe and Malawi.Key points: Including all enrolled and randomised participants in the primary analysis of a trial ensures an unbiased estimate of the intervention effect using intention-to-treat principles, and minimises the effects of confounding through balanced allocation to trial arm. Ineligible participants are sometimes enrolled, due to measurement or human error. Of 347 participants enrolled into the BREATHE trial, 11 (3.2%) were subsequently found to be ineligible based on lung function criteria. We assumed no safety risk of azithromycin treatment; their inclusion in the trial and subsequent analysis of the intervention effect therefore mirrors clinical practice. Senior trial investigators considered diurnal variations in the measurement of lung function, advantages of retaining a higher sample size and advice from the Data Safety and Monitoring Board and Trial Steering Committee, and decided to include these participants in primary analysis. We planned and reported analyses including and excluding these participants, and in our case the interpretation of treatment effect was consistent.Conclusion: The decision, by senior investigators, on whether to exclude enrolled participants, should reflect issues of safety, treatment efficacy, statistical power and measurement error. As long as decisions are made prior to finalising the statistical analysis plan for the trial, the risk of exclusions creating bias should be minimal. The decision taken should be transparently reported and a sensitivity analysis can present the opposite decision.
| S-EPMC7713189 | biostudies-literature
Project description: Not available
| S-EPMC7508503 | biostudies-literature
Project description: Not available
| S-EPMC8733489 | biostudies-literature
Project description:The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) altered the logistics of ongoing randomized controlled trials (RCTs). The need to reduce in-person research and clinical activities, however, presented an additional level of complexity in order to continue conducting RCTs that focused on the development of medications for Alcohol Use Disorder (AUD). The visits required a systematic objective evaluation from the physician and mental health professional and clinical staff, as many of the safety and efficacy assessments are self-reported. The following commentary addresses the successes and limitations our RCTs encountered during the coronavirus (COVID-19) pandemic.
| S-EPMC7832637 | biostudies-literature
Project description:Delaying disease progression and reducing the risk of mortality are key goals in the treatment of chronic kidney disease (CKD). New drug classes to augment renin-angiotensin-aldosterone system (RAAS) inhibitors as the standard of care have scarcely met their primary endpoints until recently. This systematic literature review explored treatments evaluated in patients with CKD since 1990 to understand what contemporary data add to the treatment landscape. Eighty-nine clinical trials were identified that had enrolled patients with estimated glomerular filtration rate 13.9-102.8 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio (UACR) 29.9-2911.0 mg/g, with (75.5%) and without (20.6%) type 2 diabetes (T2D). Clinically objective outcomes of kidney failure and all-cause mortality (ACM) were reported in 32 and 64 trials, respectively. Significant reductions (P < 0.05) in the risk of kidney failure were observed in seven trials: five small trials published before 2008 had evaluated the RAAS inhibitors losartan, benazepril, or ramipril in patients with (n = 751) or without (n = 84-436) T2D; two larger trials (n = 2152-2202) published onwards of 2019 had evaluated the sodium-glucose co-transporter 2 (SGLT2) inhibitors canagliflozin (in patients with T2D and UACR > 300-5000 mg/g) and dapagliflozin (in patients with or without T2D and UACR 200-5000 mg/g) added to a background of RAAS inhibition. Significant reductions in ACM were observed with dapagliflozin in the DAPA-CKD trial. Contemporary data therefore suggest that augmenting RAAS inhibitors with new drug classes has the potential to improve clinical outcomes in a broad range of patients with CKD.
| S-EPMC8799552 | biostudies-literature
Project description:INTRODUCTION:As the global epidemic continues to spread, countries have tapped effective drugs to treat new coronavirus pneumonia. The therapeutic effect of the traditional Chinese medicine Lianhua Qingwen in this new coronary pneumonia epidemic has attracted attention from all walks of life, and relevant research reports continue to appear. Therefore, we conducted a systematic review of the clinical efficacy and safety of the traditional Chinese medicine Lianhua Qingwen in the treatment of new coronavirus pneumonia (COVID-19) (referred to as "new coronary pneumonia"), and evaluated the overall level of research quality. METHODS:We searched seven databases and retrieved the Chinese Journal Full-text Database (CNKI), Vip Database (VIP), China Biomedicine (SinoMed), Wanfang Database and PubMed, Cochrane Central, EMBASE from October 2019 to May 2020 Literature references. We included randomized controlled trials (RCTs) that tested the efficacy of the traditional Chinese medicine lotus clearing plague in the treatment of new coronavirus pneumonia. The authors extracted data and independently assessed quality. We used Stata15.1 software to analyze the data of randomized trials. RESULTS:A total of 2 articles were identified, including 154 patients. All the participating patients were diagnosed with new coronavirus pneumonia (COVID-19). The meta-analysis results showed that the disappearance rate of the main clinical symptoms of Chinese medicine Lianhua Qingwen in the treatment of new coronavirus pneumonia was significantly higher than that of the control group [OR = 3.34, 95% CI (2.06, 5.44), P <0.001]; the disappearance rate of other clinical secondary symptoms is significantly higher than the control group [OR = 6.54, 95% CI (3.59, 11.90), P <0.001]. The duration of fever was significantly lower than that of the control group [OR = -1.04, 95% CI (-1.60, -0.49), P <0.001]. It is confirmed that the traditional Chinese medicine Lianhua Qingwen treatment improves the clinical effectiveness, and also has certain advantages in relieving cough and fever. CONCLUSION:The treatment of new pneumonia with traditional Chinese medicine lotus clearing plague can be used as an effective therapy to improve the clinical symptoms of new coronary pneumonia. More rigorous design, multi-center, and prospective RCTs are necessary to further determine the effectiveness and safety of the traditional Chinese medicine lotus decoction in the treatment of new pneumonia.
| S-EPMC7485773 | biostudies-literature
Project description:BackgroundThe novel coronavirus 2019 (COVID-19) pandemic has mobilized global research at an unprecedented scale. While challenges associated with the COVID-19 trial landscape have been discussed previously, no comprehensive reviews have been conducted to assess the reporting, design, and data sharing practices of randomized controlled trials (RCTs).PurposeThe purpose of this review was to gain insight into the current landscape of reporting, methodological design, and data sharing practices for COVID-19 RCTs.Data sourcesWe conducted three searches to identify registered clinical trials, peer-reviewed publications, and pre-print publications.Study selectionAfter screening eight major trial registries and 7844 records, we identified 178 registered trials and 38 publications describing 35 trials, including 25 peer-reviewed publications and 13 pre-prints.Data extractionTrial ID, registry, location, population, intervention, control, study design, recruitment target, actual recruitment, outcomes, data sharing statement, and time of data sharing were extracted.Data synthesisOf 178 registered trials, 112 (62.92%) were in hospital settings, median planned recruitment was 100 participants (IQR: 60, 168), and the majority (n = 166, 93.26%) did not report results in their respective registries. Of 35 published trials, 31 (88.57%) were in hospital settings, median actual recruitment was 86 participants (IQR: 55.5, 218), 10 (28.57%) did not reach recruitment targets, and 27 trials (77.14%) reported plans to share data.ConclusionsThe findings of our study highlight limitations in the design and reporting practices of COVID-19 RCTs and provide guidance towards more efficient reporting of trial results, greater diversity in patient settings, and more robust data sharing.
| S-EPMC7834682 | biostudies-literature
Project description: Not available
| S-EPMC7393781 | biostudies-literature
Project description:Patients with kidney disease (KD) are at increased risk for cerebrovascular disease (CVD) and CVD patients with KD have worse outcomes. We aimed to determine the representation of KD patients in major randomized controlled trials (RCTs) of CVD interventions. We searched MEDLINE for reports of major CVD trials published through February 9, 2017. We excluded trials that did not report mortality outcomes, enrolled fewer than 100 participants, or were subgroup, follow-up, or post-hoc analyses. Two independent reviewers performed study selection and data extraction. We included 135 RCTs randomizing 194,977 participants. KD patients were excluded in 48 (35.6%) trials, but were less likely to be excluded from trials of class I/II recommended interventions (n = 7; 15.9%; p = 0.001) and more likely to be excluded in trials with registered protocols (45.5% vs. 22.4%; p = 0.007). Exclusion was lower in trials supported by academic or governmental grants compared to industry or combined funding (21.2% vs. 42.0% and 47.8%; p = 0.033 and 0.028, respectively). Among trials excluding KD patients, 24 (50.0%) used serum creatinine, 7 (14.6%) used estimated glomerular filtration rate or creatinine clearance, 7 (14.6%) used renal replacement therapy, and 19 (39.6%) used non-specific kidney-related criteria. Only 4 (3.0%) trials reported baseline renal function. No trials prespecified or reported subgroup analyses by baseline renal function. Although 19 (14.1%) trials reported the incidence of acute kidney injury, no trial examined adverse event rates according to renal function. In summary, more than one third of major CVD trials excluded patients with KD, primarily based on serum creatinine or non-specific criteria, and outcomes were not stratified by renal parameters. Therefore, purposeful efforts to increase inclusion of KD patients in CVD trials and evaluate the impact of renal function on efficacy and safety are needed to improve the quality of evidence for interventions in this vulnerable population.
| S-EPMC5398672 | biostudies-literature
Project description:Background:This study assessed the short-term safety and efficacy of daprodustat (an oral hypoxia-inducible factor-prolyl hydroxylase inhibitor) to achieve a target hemoglobin in patients with anemia of chronic kidney disease (CKD). Methods:Patients (n?=?252) with Stages 3-5 CKD not receiving dialysis were enrolled in this 24-week, multicenter trial [hemoglobin entry criteria: 8-10?g/dL (Cohort 1) or 8-11?g/dL (Cohort 2) for recombinant human erythropoietin (rhEPO)-naïve participants; 9-10.5?g/dL (Cohort 1) or 9-11.5?g/dL (Cohort 2) for rhEPO users]. rhEPO-naïve participants were randomized 3:1 to daprodustat (1, 2 or 4?mg) or control (rhEPO per standard of care). rhEPO users were randomized 1:1 to daprodustat 2?mg or control. Study medication was titrated to maintain hemoglobin 9-10.5?g/dL (Cohort 1) or 10-11.5?g/dL (Cohort 2). Hemoglobin, iron metabolism markers and safety parameters were measured every 4 weeks. Results:Mean hemoglobin levels at Week 24 were 10.2?g/dL (Cohort 1) and 10.9?g/dL (Cohort 2) in the daprodustat group and 10.7?g/dL (Cohort 1) and 11.0?g/dL (Cohort 2) in the control group. Participants had hemoglobin levels within the target range a median of 82% and 66% of the time between Weeks 12 and 24 in the daprodustat and control groups, respectively. The adverse event profile was consistent with clinical events in the CKD population. Conclusions:Daprodustat effectively maintained target hemoglobin over 24 weeks in CKD patients with anemia who were rhEPO naïve or had switched from existing rhEPO therapy.
| S-EPMC6366145 | biostudies-literature